7-Chloro-6-fluoro-1-(4-methoxy-phenyl)-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid ethyl ester | 98105-88-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 7-Chloro-6-fluoro-1-(4-methoxy-phenyl)-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid ethyl ester
• 英文别名: Ethyl 7-chloro-6-fluoro-1-(4-methoxyphenyl)-4-oxoquinoline-3-carboxylate
• CAS: 98105-88-5
• 化学式: C₁₉H₁₅ClFNO₄
• 分子量: 375.784
• InChiKey: WSSDXBOQLARQTE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  55.8
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  7-Chloro-6-fluoro-1-(4-methoxy-phenyl)-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid ethyl ester 在 sodium hydroxide 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 生成 7-chloro-1-p-methoxyphenyl-6-fluoro-1,4-dihydro-4-oxo-quinoline-3-carboxylic acid
  参考文献：
  名称：

  新型N1-芳基取代喹诺酮类抗菌药的合成及生物活性

  摘要：

  已经合成了一系列在 N1 苯环上具有系统变化取代的喹诺酮类药物。已经确定了三个亲脂性描述符（log K、log P、Rm）和 pKa 值以及微生物活性：三种革兰氏阳性菌和三种革兰氏阴性菌的八种不同菌株的 MIC 值以及测定 DNA 超螺旋（IC90 和 IC100）的抑制浓度。从主成分和 QSAR 分析可以推导出与全细胞系统相关的抗菌活性与电子特性以及苯环上的取代基长度之间的关系。无细胞系统中的活性受替代品的亲脂性和宽度控制。据推测，喹诺酮类药物在以极性氨基酸为特征的 DNA 促旋酶-DNA 复合物中占据特定位置。这与突变回旋酶研究的结果一致。

  DOI：

  10.1002/ardp.19963290403
• 作为产物：
  描述：

  2,4-二氯-5-氟-Β-氧代苯丙酸乙酯 在 乙酸酐 、 sodium hydride 作用下， 以 乙二醇二甲醚 、 二氯甲烷 为溶剂， 反应 5.5h， 生成 7-Chloro-6-fluoro-1-(4-methoxy-phenyl)-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid ethyl ester
  参考文献：
  名称：

  Synthesis and structure-activity relationships of novel arylfluoroquinolone antibacterial agents

  摘要：

  A series of novel arylfluoroquinolones has been prepared. These derivatives are characterized by having a fluorine atom at the 6-position, substituted amino groups at the 7-position, and substituted phenyl groups at the 1-position. Structure-activity relationship (SAR) studies indicate that the in vitro antibacterial potency is greatest when the 1-substituent is either p-fluorophenyl or p-hydroxyphenyl and the 7-substituent is either 1-piperazinyl, 4-methyl-1-piperazinyl, or 3-amino-1-pyrrolidinyl. The electronic and spatial properties of the 1-substituent, as well as the steric bulk, play important roles in the antimicrobial potency in this class of antibacterials. As a result of this study, compounds 45 and 41 were found to possess excellent in vitro potency and in vivo efficacy.

  DOI：

  10.1021/jm00149a003

文献信息

• NORITA, XIROKADZU;ONISI, JOSINORI;NITTA, ATSUSI;NAGAKI, XIDEHESI;KITAYAMA+
  作者：NORITA, XIROKADZU、ONISI, JOSINORI、NITTA, ATSUSI、NAGAKI, XIDEHESI、KITAYAMA+

  DOI：——

  日期：——
• Synthesis and structure-activity relationships of novel arylfluoroquinolone antibacterial agents
  作者：Daniel T. W. Chu、Prabhavathi B. Fernandes、Akiyo K. Claiborne、Eva Pihuleac、Carl W. Nordeen、Robert E. Maleczka、Andre G. Pernet

  DOI：10.1021/jm00149a003

  日期：1985.11

  A series of novel arylfluoroquinolones has been prepared. These derivatives are characterized by having a fluorine atom at the 6-position, substituted amino groups at the 7-position, and substituted phenyl groups at the 1-position. Structure-activity relationship (SAR) studies indicate that the in vitro antibacterial potency is greatest when the 1-substituent is either p-fluorophenyl or p-hydroxyphenyl and the 7-substituent is either 1-piperazinyl, 4-methyl-1-piperazinyl, or 3-amino-1-pyrrolidinyl. The electronic and spatial properties of the 1-substituent, as well as the steric bulk, play important roles in the antimicrobial potency in this class of antibacterials. As a result of this study, compounds 45 and 41 were found to possess excellent in vitro potency and in vivo efficacy.
• Syntheses and Biological Activities of NewN1-Aryl Substituted Quinolone Antibacterials
  作者：Jens Jürgens、Holger Schedletzky、Peter Heisig、Joachim K. Seydel、Bernd Wiedemann、Ulrike Holzgrabe

  DOI：10.1002/ardp.19963290403

  日期：——

  A series of quinolones with a systematically varied substitution at the phenyl ring at N1 has been synthesized. Three lipophilicity descriptors (log K, log P, Rm) and the pKa values have been determined as well as the microbiological activity: The MIC values for eight different strains of three Gram‐positive and three Gram‐negative species and the inhibitory concentrations of DNA supercoiling (IC90

  已经合成了一系列在 N1 苯环上具有系统变化取代的喹诺酮类药物。已经确定了三个亲脂性描述符（log K、log P、Rm）和 pKa 值以及微生物活性：三种革兰氏阳性菌和三种革兰氏阴性菌的八种不同菌株的 MIC 值以及测定 DNA 超螺旋（IC90 和 IC100）的抑制浓度。从主成分和 QSAR 分析可以推导出与全细胞系统相关的抗菌活性与电子特性以及苯环上的取代基长度之间的关系。无细胞系统中的活性受替代品的亲脂性和宽度控制。据推测，喹诺酮类药物在以极性氨基酸为特征的 DNA 促旋酶-DNA 复合物中占据特定位置。这与突变回旋酶研究的结果一致。